Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors
Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors
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DOI：
10.1016/j.molcel.2006.03.008
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发表时间：
2006-04-07
期刊：
影响因子：
16
通讯作者：
Vuister, GW
中科院分区：
文献类型：
--
作者：
Hilge, M;Aelen, J;Vuister, GW
质膜Na+/Ca ~（2+）交换器（NCX）是心肌细胞Ca ~（2+）排出的主要机制。Na+和Ca 2+离子与其大的胞质环的结合调节交换器的离子转运。我们确定了两个Ca 2+结合结构域（CBD 1和CBD 2）的溶液结构，它们与α-连环蛋白样结构域（CLD）一起形成调节交换环。CBD 1和CBD 2在Ca 2+结合状态下非常相似，并描述了Calx-β基序。引人注目的是，在没有Ca 2+的情况下，CBD 1的上半部分展开，而CBD 2保持其结构完整性。与对Ca 2+的7倍更高的亲和力一起，这表明CBD 1是主要的Ca 2+传感器。任一结构域中的特定点突变在很大程度上允许其功能的互换，并揭示了NCX中Ca 2+传感的潜在机制。
The plasma membrane Na+/Ca2+ exchanger (NCX) is almost certainly the major Ca2+ extrusion mechanism in cardiac myocytes. Binding of Na+ and Ca2+ ions to its large cytosolic loop regulates ion transport of the exchanger. We determined the solution structures of two Ca2+ binding domains (CBD1 and CBD2) that, together with an alpha-catenin-like domain (CLD), form the regulatory exchanger loop. CBD1 and CBD2 are very similar in the Ca2+ bound state and describe the Calx-beta motif. Strikingly, in the absence of Ca2+ the upper half of CBD1 unfolds while CBD2 maintains its structural integrity. Together with a 7-fold higher affinity for Ca2+ this suggests that CBD1 is the primary Ca2+ sensor. Specific point mutations in either domain largely allow the interchange of their functionality and uncover the mechanism underlying Ca2+ sensing in NCX.